Adipose Tissue–Derived Stromal Cells Inhibit TGF-1–Induced Differentiation of Human Dermal Fibroblasts and Keloid Scar–Derived Fibroblasts in a Paracrine Fashion
Adipose Tissue–Derived Stromal Cells Inhibit TGF-1–Induced Differentiation of Human Dermal Fibroblasts and Keloid Scar–Derived Fibroblasts in a Paracrine Fashion
复制标题
DOI：
10.1097/prs.0000000000000504
复制
发表时间：
2014-10
影响因子：
3.6
通讯作者：
Maroesjka Spiekman;Ewa Przybyt;J. Plantinga;S. Gibbs;B. van der Lei;M. Harmsen
中科院分区：
文献类型：
--
作者：
Maroesjka Spiekman;Ewa Przybyt;J. Plantinga;S. Gibbs;B. van der Lei;M. Harmsen
背景：脂肪组织来源的基质细胞可促进伤口愈合和皮肤再生。目前尚不清楚它们是否以及如何影响真皮疤痕。作者假设，脂肪组织来源的基质细胞可抑制由疤痕形成关键因子（即转化生长因子 (TGF)-）诱导的真皮成纤维细胞的不良分化。方法：将 TGF-1 处理的成人真皮成纤维细胞和瘢痕疙瘩衍生的成纤维细胞与脂肪组织衍生的基质细胞条件培养基一起孵育，并评估其增殖和分化，特别是胶原蛋白的产生、SM22 的表达以及肥大和收缩性的发展。结果：脂肪组织来源的基质细胞条件培养基消除了 TGF-1 诱导的成人真皮成纤维细胞增殖。同时，该培养基降低了TGF-1处理的成人真皮成纤维细胞的SM22基因和蛋白表达，并且它们的收缩性也降低。此外，该培养基强烈降低了胶原蛋白 I 和 III 基因及其相应蛋白质的转录。相反，它通过刺激基质金属蛋白酶 (MMP)-1、MMP-2 和 MMP-14 的基因表达，使基质周转的平衡转向降解，而 MMP-2 活性也上调。即使在终末期肌成纤维细胞（即瘢痕疙瘩衍生的成纤维细胞）中，脂肪组织衍生的基质细胞条件培养基也能抑制 TGF-1 诱导的肌成纤维细胞收缩和 III 型胶原基因表达。结论：作者表明，脂肪组织来源的基质细胞以旁分泌方式抑制 TGF-1 诱导的成人真皮成纤维细胞的不良分化和功能，以及 TGF-1 诱导的瘢痕疙瘩来源的成纤维细胞的收缩。
Background: Adipose tissue–derived stromal cells augment wound healing and skin regeneration. It is unknown whether and how they can also influence dermal scarring. The authors hypothesized that adipose tissue–derived stromal cells inhibit adverse differentiation of dermal fibroblasts induced by the pivotal factor in scarring, namely, transforming growth factor (TGF)-. Methods: TGF-1–treated adult human dermal fibroblasts and keloid scar–derived fibroblasts were incubated with adipose tissue–derived stromal cell–conditioned medium and assessed for proliferation and differentiation, particularly the production of collagen, expression of SM22, and development of hypertrophy and contractility. Results: TGF-1–induced proliferation of adult human dermal fibroblasts was abolished by adipose tissue–derived stromal cell–conditioned medium. Simultaneously, the medium reduced SM22 gene and protein expression of TGF-1–treated adult human dermal fibroblasts, and their contractility was reduced also. Furthermore, the medium strongly reduced transcription of collagen I and III genes and their corresponding proteins. In contrast, it tipped the balance of matrix turnover to degradation through stimulating gene expression of matrix metalloproteinase (MMP)-1, MMP-2, and MMP-14, whereas MMP-2 activity was up-regulated also. Even in end-stage myofibroblasts (i.e., keloid scar–derived fibroblasts), adipose tissue–derived stromal cell–conditioned medium suppressed TGF-1–induced myofibroblast contraction and collagen III gene expression. Conclusion: The authors show that adipose tissue–derived stromal cells inhibit TGF-1–induced adverse differentiation and function of adult human dermal fibroblasts and TGF-1–induced contraction in keloid scar–derived fibroblasts, in a paracrine fashion.